|Title||Receptor-mediated and lectin-like activities of carp (Cyprinus carpio) TNF-alpha.|
|Publication Type||Journal Article|
|Year of Publication||2009|
|Authors||Forlenza, M., S. Magez, J. P. Scharsack, A. Westphal, H. F. J. Savelkoul, and G. F. Wiegertjes|
|Date Published||2009 Oct 15|
|Keywords||Amino Acid Sequence, Animals, Carps, Cell Movement, Endothelial Cells, Fish Diseases, Gene Expression, Lectins, Molecular Sequence Data, Pentoxifylline, Phagocytes, Phagocytosis, Phosphodiesterase Inhibitors, Recombinant Proteins, Sequence Alignment, Trypanosomiasis, Tumor Necrosis Factor-alpha, Up-Regulation|
Functional characterization of TNF-alpha in species other than mammalian vertebrates is limited, and TNF-alpha has been studied in a limited number of fish species, primarily in vitro using recombinant proteins. Studies on TNF-alpha from different fish species so far pointed to several inconsistencies, in particular with respect to some receptor-mediated activities of fish TNF-alpha, such as the ability to directly activate phagocytes. In the present study a comprehensive analysis of in vitro as well as in vivo biological activities of two isoforms of carp TNF-alpha was performed. Our results show that carp TNF-alpha directly primes carp phagocytes and indirectly promotes typical receptor-mediated activities such as phagocyte activation by acting via endothelial cells. Additionally, for the first time in nonmammalian vertebrate species, the lectin-like activity of fish TNF-alpha homologs was investigated. Our results show an evolutionary conservation of function of this receptor-independent activity of TNF-alpha not only in cyprinid fish, but also in perciform and salmonid fish. The role of TNF-alpha in vivo, during infections of carp with the blood parasite Trypanoplasma borreli, was examined using three fundamentally different but complementary approaches: (1) inhibition of TNF-alpha expression, (2) overexpression of TNF-alpha, and (3) inhibition of shedding of membrane-bound TNF-alpha. Our results show that, also in fish, a tight regulation of TNF-alpha expression is important, since depletion or excess of TNF-alpha can make an important difference to survival of infection. Finally, we demonstrate a crucial protective role for membrane-bound TNF-alpha, which has a yet unexploited function in fish.
|Alternate Journal||J. Immunol.|